multiple myeloma. a

Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients...

Although multiple myeloma (MM) is a neoplasm that leads affected individuals to death, little is known about why some patients survive much longer than others. In this context, we investigated the transcriptomic profile of bone marrow hematopoietic stem cells obtained from MM patients and compared the clinical outcomes of death and survival six months after bone marrow transplantation. The leukapheresis products of 39 patients with MM eligible for autologous transplantation were collected and analyzed. After extraction, the RNA was analyzed using the GeneChip Human Exon 1...

Multiple Myeloma (MM) is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in about 50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Since these genes are part of our routine next-generation sequencing (NGS) panel, we analyzed >10,000 patients with different plasma cell disorders in order to describe the RAS/RAF landscape. In this large cohort of patients, almost 61% of the patients presented a RAS/RAF mutation at diagnosis or relapse, but much lower frequencies in pre-symptomatic cases...

BACKGROUND: Ruxolitinib (RUX), an orally administered selective Janus kinase 1/2 inhibitor, has received approval for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. We have previously demonstrated the anti-multiple myeloma effects of RUX alone and in combination with the immunomodulatory agent lenalidomide (LEN) and glucocorticosteroids both pre-clinically and clinically. OBJECTIVE: This study aims to evaluate whether LEN can achieve clinical activity among patients with multiple myeloma progressing on the combination of RUX and methylprednisolone (MP)...

Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells...

Chimeric antigen receptor T-cell (CAR-T) therapy has significantly impacted treatment algorithms and clinical outcomes for a variety of patients with hematologic malignancies over the past decade. The field of cellular immunotherapy is currently experiencing a rapid expansion of the number of patients eligible for CAR-T therapies as approvals are being seen in earlier lines of therapy. With the expanded patients eligible for these therapies, more treatment centers will be necessary to keep up with demand. Building a cellular therapy program can be a daunting task, and therefore, we present our experience with building a clinical cellular therapy program...

Period circadian regulator 3 (PER3) functions as a tumor suppressor in various cancers. However, the role of PER3 in multiple myeloma (MM) has not been reported yet. Through this study, we aimed to investigate the potential role of PER3 in MM and the underlying mechanisms. RT-qPCR and western blotting were used to determine the mRNA and protein expression levels of PER3. Glyoxylate reductase 1 homolog (GLYR1) was predicted to be a transcription factor of PER3. The binding sites of GLYR1 on the promoter region of PER3 were analyzed using UCSC and confirmed using luciferase and chromatin immunoprecipitation assays...

Immunotherapies have significantly improved outcomes in patients with multiple myeloma yet maintaining a durable response in heavily pretreated patients remains challenging. Therapies that target B cell maturation antigen (BCMA) provide additional treatment options in patients whose disease becomes refractory to several drug classes in early lines of therapy. Clinical trial data from selected patient populations and controlled settings are complemented by real-world data (RWD) from actual clinical practice...

Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these tumors from other round cells tumors including lymphoma, cutaneous histiocytoma, and amelanotic melanomas. CEMPs are characterized by widespread immunoreactivity for multiple myeloma 1 (MUM1) antigen and λ light chains, while the melanocytic marker melan-A has been reported to yield negative results. Here, 33 randomly selected CEMPs, 20 melanocytomas, and 20 malignant melanomas were immunohistochemically tested for MUM1, melan-A, and PNL2...

Monoclonal proteins are common, with a prevalence in the United States around 5% and the incidence increases with age. Although most patients are asymptomatic, the vast majority of cases are caused by a clonal plasma cell disorder. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions with variable risk of progression to multiple myeloma (MM). In recent years, significant progress has been made to better understand the factors that lead to the development of symptoms and progression to myeloma...

Mantle cell lymphoma (MCL) is a rare, incurable non-Hodgkin's lymphoma characterized by naive B cells infiltrating the lymphoid follicle's mantle zone. A key feature of MCL is the cytogenetic abnormality t(11;14) (q13:q14), found in 95% of cases, leading to Cyclin D1 overexpression resulting in uncontrolled cell cycle progression and genetic instability. Occasionally, Cyclin D2 or D3 overexpression can substitute for Cyclin D1, causing similar effects. The transcription factor SOX11 is a hallmark of classical Cyclin D1-positive MCL and also in cases without the typical t(11;14) abnormality, making it an important diagnostic marker...

The introduction of daratumumab has improved treatment outcomes for multiple myeloma (MM). However, infectious complications are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases, and few describe patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy...

Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy...

Tailoring optimal treatment for individual cancer patients remains a significant challenge. To address this issue, we developed PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology), a precision oncology computational pipeline. Our approach uses publicly available matched bulk and single-cell (sc) expression profiles from large-scale cell-line drug screens. These profiles help build treatment response models based on patients' sc-tumor transcriptomics. PERCEPTION demonstrates success in predicting responses to targeted therapies in cultured and patient-tumor-derived primary cells, as well as in two clinical trials for multiple myeloma and breast cancer...

Developing prognostic tools specifically for patients themselves represents an important step in empowering patients to engage in shared decision-making. Incorporating patient-reported outcomes may improve the accuracy of these prognostic tools. We conducted a retrospective population-based study of transplant-ineligible (TIE) patients with multiple myeloma (MM) diagnosed between January 2007 and December 2018. A multivariable Cox regression model was developed to predict the risk of death within 1-year period from the index date...

Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukaemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose...

BACKGROUND: Daratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the γ-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference. METHODS: An up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples...

BACKGROUND: Preoperative diagnosis of gallbladder amyloidosis is usually difficult. In our case, the patient exhibited gallbladder dyskinesia, which led us to suspect cholecystic amyloidosis. We were able to safely perform surgery before cholecystitis onset. CASE PRESENTATION: A 59-year-old male patient with a history of multiple myeloma and cardiac amyloidosis presented to our hospital with a chief complaint of epicardial pain. Abdominal ultrasonography and computed tomography revealed an enlarged gallbladder and biliary sludge without any specific imaging findings of cholecystitis...

BACKGROUND: Natural killer cells (NKs) may be involved in multiple myeloma (MM) progression. The present study elucidated the correlation between NKs and the progression of MM using single-cell binding transcriptome probes to identify NK cell-related biomarkers. METHODS: Single-cell analysis was performed including cell and subtype annotation, cell communication, and pseudotime analysis. Hallmark pathway enrichment analysis of NKs and NKs-related differentially expressed genes (DEGs) were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction (PPI) networks...

Solitary bone plasmacytoma (SBP) is a rare hematological malignancy that usually occurs in the spine and rarely in the skull. It rarely presents in the skull base, but presenting symptoms are associated with cranial nerve involvement depending on the site of the disease. We present the case of a 61-year-old man with an unusual presentation of hoarseness secondary to vocal fold palsy. Imaging showed a large bony lesion in the temporo-occipital region with involvement of the jugular foramen. Further detailed diagnostic procedures confirmed SBP of the skull base...